SPRITE: A New Technique For Mapping DNA In Our Nuclei

Researchers at the California Institute of Technology led by NYSCF – Robertson Investigator Mitchell Guttman, PhD, have developed a new tool called SPRITE to uncover how cells organize their DNA within the nucleus.

Each of our cells has a nucleus about 10 micrometers wide (smaller than the width of a strand of hair). Tightly packed into this nucleus is 6 feet of DNA containing our genetic blueprint.

It may seem like the position of DNA within the nucleus doesn’t matter, but the way our DNA folds isn’t random—it dictates how a cell works and survives. If DNA folds incorrectly, it can lead to disease. This is one of the reasons it is important to understand the structure of the nucleus: it gives us a better idea of how to prevent DNA from undergoing these harmful changes.

Also packed into the nucleus are structures called nuclear bodies, which help turn certain genes on and off. The activation and inactivation of genes is an essential process that guides stem cells to become specialized cells (such as neurons, liver cells, muscle cells, etc.). However, nuclear bodies must first search through the DNA to find the genes they regulate.

To better understand how DNA is structured in the nucleus and how this structure contributes to a cell’s development and activity, the researchers developed a tool called SPRITE (short for Split-Pool Recognition of Interactions by Tag Extension). This tool marks clusters of molecules within the nucleus with a certain tag that acts like a barcode. Once the researchers break open the nucleus, they can then discern which molecules were interacting with each other by observing which ones carry the same barcode.

The team found that certain genes tended to cluster around certain nuclear bodies. Inactive genes were found located around a type of nuclear body that suppresses gene activity while active genes were found located around a type of nuclear body that promotes gene activity. This suggests that DNA organizes itself in a manner so that genes that need to be suppressed are clustered together and genes that need to be activated are clustered together, allowing nuclear bodies to easily access and control them without combing through all 6 feet of DNA to pick out individual genes.

For more information, check out the paper in Cell or the press release from the California Institute of Technology.